Haem Flashcards
(37 cards)
What is Sickle cell disease?
Sickle cell anaema is a genetic condition where normal haemoglobin has a tendency to form abnormal haemoglobin molecules (HbS) upon deoxygenation.
It is common amongst individuals of central and western African descent, offering increased resistance to malaria.
How does sickle cell disease cause hyposplenism?
In addition, sickle cells commonly sequester in the spleen and undergo phagocytosis by the reticular endothelial system leading to extravascular haemolysis.
Commonly this leads to splenic congestion and splenomegaly. The spleen is necessary for phagocytosis of encapsulated bacteria. Consequently, due to a compromised spleen, there is reduced immune function and individuals with sickle cell disease are prone to bacteraemia.
What is the most common acute presentation of sickle cell disease?
Painful vaso occlusive crises are the most common acute presentation of sickle cell anaemia, caused primarily by microvascular obstruction due to cellular sickling, which may be triggered by local hypoxia (e.g. in cold weather).
What are the features of an acute cell crisis?
In contrast, acute chest crises are the most dangerous acute presentation (3% mortality; cause of 25% of sickle cell related deaths). The cause is often unknown (may be infectious), but patients present with tachypnoea, wheeze, and cough, with hypoxia and pulmonary infiltrates.
What is the screening for sickle cell anaemia?
Sickle cell anaemia in the UK is typically diagnosed postnatally (national screening programme), but otherwise presents with progressive anaemia in early life as levels of foetal haemoglobin (which contains no beta-globin component) fall.
What are the investigations of sickle cell disease?
Investigations may show a microcytic anaemia with variable degrees of haemolysis (reticulocytosis and unconjugated hyperbilirubinemia may be noted).
Typical blood film findings include: characteristic sickle cells, target cells, reticulocytosis with polychromasia and features of functional hyposplenism (Howell-Jolly bodies, nucleated red blood cells).
Definitive diagnosis is with haemoglobin electrophoresis +/- genetic testing.
What is the management of sickle cell crisis?
Conservative management involves high flow oxygen, IV fluids and analgesia. Top-up transfusions may be required in severe cases. IV antibiotics should also be given to treat underlying cause and if Hb below 30% of normal, packed red cell transfusion to avoid multi organ failure
What is the management of chronic sickle cell disease?
Hydroxycarbamide if frequent crises which increases fetal haemoglobin concentrations
Regular exchange transfusions may be required for severe anaemia
Regular exchange transfusions may be required for severe anaemia
What are the complications of sickle cell disease?
Splenic infarction and subsequent immunocompromise
Sequestration crisis
Osteomyelitis
Stroke
Poor growth
Chronic renal disease
Gallstones
Retinal disorders
Pulmonary fibrosis and pulmonary hypertension
Iron overload: from repeated blood transfusions
Red cell aplasia (due to parvovirus B19 infection in patients with chronic haemolytic anaemia)
What is Haemolytic anaemia?
Haemolytic anaemia describes anaemia caused by the destruction or “lysis” of red blood cells. There are many diverse causes, both hereditary and acquired.
In addition to the distinction between hereditary and acquired causes, haemolytic anaemia can be classified based on the location of the haemolysis: intravascular or extravascular.
Another distinction is autoimmune (Coombs positive) and non-autoimmune (Coombs negative) haemolytic anaemia.
What are the general biochemical features of haemolytic anaemia?
Haemolytic anaemia is associated with low haemoglobin, high bilirubin (unconjugated) and may be associated with reticulocytosis, raised LDH and raised urinary urobilinogen.
What are the pathophysiological features of Intravascular haemolytic anaemia?
Intravascular haemolysis occurs in the blood stream, resulting in release of cellular contents (in particular haemoglobin) into the circulation.
This excess of haemoglobin is dealt with in many ways: combines with haptoglobin, combines with albumin (methaemalbuminaemia), loss in the urine (haemoglobinuria), and stored in tubular epithelial cells as haemosiderin and shed into the urine (hemosiderinuria).
What are the causes of Intravascular haemolytic anaemia?
Intrinsic cellular injury (e.g. glucose-6-phosphate deficiency - G6PD)
Intravascular complement mediated lysis (some autoimmune haemolytic anaemias
Paroxysmal nocturnal haemoglobinuria and acute transfusion reactions)
Mechanical injury (Microangiopathic haemolytic anaemia and cardiac valves)
Autoimmune haemolytic anaemia
What are the features of a G6P deficiency?
G6PD is an X-linked recessive red-cell enzyme disorder which may present in the neonatal period with jaundice, or later in life with episodic intravascular haemolysis following exposure to oxidative stressors.
What are the triggers for G6P deficiency?
Intercurrent illness or infection (often forgotten)
Fava beans: the disease was historically known as favism
Henna
Medications: primaquine, sulfa-drugs, nitrofurantoin, dapsone, and NSAIDs/Aspirin
What are the investigations and management of G6PD?
The blood film typically shows Heinz bodies and bite cells, and the diagnostic test is a G6PD enzyme assay.
Treatment involves avoidance of precipitants, and some patients may rarely require transfusions.
What is the pathophysiology of extravascular haemolytic anaemia?
Extravascular haemolysis occurs in the reticuloendothelial system (the spleen and liver) and is therefore not associated with dramatic release of free haemoglobin into the circulation. Splenomegaly and hepatomegaly are typical.
Causes include:
Abnormal red blood cells (sickle cell anaemia and hereditary spherocytosis)
Normal cells marked by antibodies for splenic phagocytosis.
What is Hereditary spherocytosis?
Hereditary spherocytosis is an autosomal dominant condition, seen in northern European populations, caused by mutations in structural red cell membrane proteins.
Abnormal sections of membrane are removed by the spleen, resulting in a reduced surface area to volume ratio and causing spherical distortion of cells (seen as spherocytes on blood film).
Eventually, as more membrane is removed, the cells haemolyse (extravascular haemolysis) and are removed from circulation in the spleen.
It typically presents with neonatal or childhood onset jaundice/anaemia, and splenomegaly.
If mild, patients may be managed conservatively with folic acid supplementation. If severe, splenectomy before the age of 5 years is essentially curative.
What is the key investigation in autoimmune haemolytic anaemia?
To elucidate the aetiology of the haemolytic anaemia, the direct Coombs test may be used. It is a test for autoimmune haemolytic anaemia (AIHA).
Patients with AIHA have antibodies directed against cell surface markers on the red blood cell. The Coombs test uses antibodies against these autoantibodies to cross link and agglutinate the red cells.
What are the the two types of coombs positive haemolytic anaemia?
Two major groups of Coombs-positive AIHA are known: warm and cold autoimmune haemolytic anaemia.
Warm AIHA is an IgG mediated extravascular haemolytic disease in which the spleen tags cells for splenic phagocytosis
Causes are:
Idiopathic
Lymphoproliferative neoplasms (CLL and lymphoma)
Drugs including methyldopa
SLE
Cold AIHA is an IgM-mediated haemolytic disease in which IgM fixes complement causing direct intravascular haemolysis (also known as cold agglutinins)
causes are:
Idiopathic
Post-infectious haemolytic anaemias: occurring 2-3 weeks after infection (examples include EBV and mycoplasma)
What are coombs negative haemolytic anaemias?
Acquired haemolytic anaemias that are Coombs negative are a large group of diverse haemolytic disorders.
Microangiopathic haemolytic anaemia
Paroxysmal nocturnal haemoglobinuria
Physical lysis of red cells e.g. malaria
Haemolytic uraemic syndrome (E. coli 0157:H7)
Infectious causes DIC (such as fulminant meningococcemia)
What is microangiopathic haemolytic anaemia?
Microangiopathic haemolytic anaemia is an intravascular haemolytic disorder caused by physical lysis of red cells by deposited fibrin strands, resulting in the presence of schistocytes (fragments of red blood cells) on the blood film.
It may be isolated, or occur in association with a thrombotic microangiopathy syndrome (such as haemolytic uraemic syndrome and thrombotic thrombocytopenia purpura), or in severe cases, disseminated intravascular coagulation.
What are the features of paroxysmal nocturnal haemoglobinuria?
Paroxysmal nocturnal haemoglobinuria is a rare acquired stem cell disorder of unknown aetiology.
An abnormal surface glycoprotein expressed on a subclone of red blood cells marks these cells for complement mediated haemolysis – severity depends on the size of this subclone.
Patients present in early adulthood with nocturnal episodes of intravascular haemolysis (it is not known why this occurs at night), and may be associated with other stem cell defects and increased risk of thrombosis (via an effect on complement mediated platelet aggregation). Diagnosis is with flow cytometry.
What causes physical lysis of red cells?
Physical lysis of red cells may occur in falciparum malaria and babesiosis (diseases in which the parasite grows in the red cell cytoplasm), and in patients with prosthetic heart valves.